1. Field of the Invention
This invention relates to a process for producing aphidicolin, and more particularly to a process for producing aphidicolin by culturing microorganisms.
2. Prior Art
Aphidicolin is a sparingly water-soluble substance having a tetracyclic diterpenetetraol represented by the following formula: ##STR1## which is obtained from Verticillium lecanii, a kind of mold, and has been found to have an antiviral effect. Aphidicolin also has a high specific inhibiting action on DNA polymerase .alpha. originating from eucaryotic cells, and thus has been used to identify the type of DNA polymerase originating from eucaryotic cells. Furthermore, aphidicolin has no such effect on DNA polymerase originating from procaryotic cells excluding specific viruses and is used mainly in the analysis of DNA replication and repair mechanisms. Furthermore, aphidicolin is known to have an antitumor effect, an anti-virus effect and a plant seed growth-inhibiting effect and thus its utilization in these fields has been contemplated.
However, aphidicolin has a low production efficiency and thus is commercially available as a very expensive biochemical reagent (for example, the current merket price is 5,500 yen per mg). It is also reported to produce aphidicolin by using other fungi than the Cephalosporium aphidicola, for example, Phoma betae [Japanese Patent Application Kokai (Laid-open) No. 58-220690], Harziella entomophila [Agri. Biol. Chem., 42, No. 8, page 1611 (1978)], Onychophora coprophila [Trans. Br. Mycol. Soc., 83, No. 1, page 149 (1984)], Nigrospora sphaerica [Can. J. Microbiol., 20, page 416 (1974)], etc., but their productivity of aphidicolin is low and not satisfactory. For example, only 120 mg of aphidicolin is isolated from 1.5 l of a culture medium of Nigrospora sphaerica.